Cu2+-Anthraquinone Complexes : Formation, Interaction with DNA, and Biological Activity

摘要

Growth inhibition potency of the anthraquinones, anthraquinone-1,5-disulfonic acid and carminic acid, for Sarcoma 180 and L1210 leukemia cells in vivo and in vitro, was induced by the divalent transition metal ion, Cu2+. On the other hand spectroscopic titration data show that the anthraquinone drugs form Cu2+ chelate complexes (carminic acid : Cu2+ = 1 : 6; anthraquinone-1,5-disulfonic acid : Cu2+ = 1 : 3). Furthermore the Cusup>2+-drug complexes associate with DNA to form the Cu2+-anthraquinone-DNA ternary complexes. The formation of the complexes was further supported by the H2O2-dependent DNA degradation, which can be inhibited by ethidium bromide, caused by the Cu2+-drug complexes. It is likely that the Cu2+-mediated cytotoxicity of the anthraquinone drugs is related with the Cu2+-mediated binding of the anthraquinone drugs to DNA and DNA degradation.